Immune development in early life (IDEAL) shapes vaccine response, respiratory infectious diseaseand asthma
生命早期的免疫发育 (IDEAL) 影响疫苗反应、呼吸道传染病和哮喘
基本信息
- 批准号:10589800
- 负责人:
- 金额:$ 154.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-10 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAdjuvantAdultAfricaAgeAsthmaAustralasiaBacteriaBioinformaticsBiological AssayBiological MarkersBiological ModelsBirthBlood DonationsBlood VolumeCellsChildhoodClinicalCommunicable DiseasesCoupledDataDevelopmentDiseaseEnrollmentEpigenetic ProcessGoalsGreekGrowthHealthHumanHuman bodyImmuneImmune systemImmunityImmunologicsImmunomodulatorsIn VitroIndividualInfantInfectionInnate Immune ResponseInterventionKnowledgeLifeLiquid substanceMeasuresMediatingMedicalMemoryModelingMolecularMolecular ProfilingMucous MembraneNewborn InfantNorth AmericaNoseOrganPRTN3 genePathway interactionsPatternPediatric cohortPhenotypePhysiologicalPlasmaPositioning AttributePredispositionPrognostic MarkerProtective AgentsProteinsProteomicsPublishingResistanceRespiratory DiseaseRespiratory Tract InfectionsRiskSamplingShapesSystemSystems BiologyTestingTrainingTranslatingVaccinesValidationadaptive immune responseage relatedbiobankbioinformatics toolclinical phenotypecohortexperiencegut microbiomehigh riskin silicoin uteroin vitro Modelinfancyinfection riskinsightinter-individual variationmetabolomicsmicrobiomemultiple omicsnovel strategiespredictive markerpreventprogramsprospectiverespiratoryresponserisk predictionspecific biomarkerstoolvaccine response
项目摘要
PROJECT SUMMARY
To date, efforts to define and apply precision endotyping has been limited to studies of adults. However,
immune development in early life (IDEAL) is dynamic and varies between individuals suggesting that
endotypes corresponding to distinct pathophysiological mechanisms will be age-dependent. We propose
therefore a novel approach in which we will study well-defined longitudinal childhood cohorts and use in silico
integrative analyses of existing and prospectively collected data coupled with age-specific human in vitro model
systems to identify agents that redirect IDEAL away from disease endotypes towards those associated with
health. We have selected three clinical endpoints to correlate with systems biology data to identify IDEAL
endotypes: a) vaccine responsiveness, as vaccines are the most important biomedical intervention to
reduce childhood disease; b) respiratory infection which represents the greatest burden of childhood
infectious disease; and c) asthma, an immune-mediated respiratory disease which manifests in
childhood and results in substantial health burden. Each of these endpoints demonstrates substantial
inter-individual variability enabling powerful systems biology tools to extract meaningful correlations. We
will harmonize and study an IDEAL Meta-Cohort (IMC) comprised of longitudinal childhood cohorts
enrolled in North America, Africa and Australasia. Our Clinical Core in Rochester, NY, is nationally
prominent in the study of childhood immune ontogeny. Project (PR) 1 will employ cutting edge, cross-
platform integrative bioinformatics tools to identify endotypes associated with clinical endpoints. PR2, will
apply epigenetic analysis tools to the same samples and translate to host immune parameters the in
silico-derived signatures. In PR3, key endotype-associated biomarkers and pathways will be dissected in
vitro to establish cause and effect and identify agents (e.g., proteins, metabolites, adjuvants, vaccines) that
may redirect IDEAL away from unfavorable endotypes and towards favorable ones. We have optimized
sample-sparing assays to enable systems biology in infants and our published preliminary data
demonstrate feasibility, robust IDEAL, and suggest distinct signatures by clinical status. Our cross-
platform validation and correlation with endotypes correlating with clinical phenotypes will identify
predictive/actionable biomarkers by i) characterizing IDEAL and microbiome in systemic/mucosal
compartments (Overall Aim 1), ii) identifying endotype-specific biomarkers (Overall Aim 2), identifying in
vitro interventions that re-direct IDEAL endotypes towards health (Overall Aim 3). Overall, we will enhance
and accelerate discovery of new approaches to predict and prevent childhood disease.
项目总结
项目成果
期刊论文数量(0)
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{{ truncateString('OFER LEVY', 18)}}的其他基金
Immune development in early life (IDEAL) shapes vaccine response, respiratory infectious diseaseand asthma
生命早期的免疫发育 (IDEAL) 影响疫苗反应、呼吸道传染病和哮喘
- 批准号:
10435035 - 财政年份:2022
- 资助金额:
$ 154.65万 - 项目类别:
Project 3: In vitro modeling to define mechanisms of childhood vaccine response, susceptibility to respiratory infectious disease and asthma
项目 3:体外建模以确定儿童疫苗反应、呼吸道传染病和哮喘易感性机制
- 批准号:
10589826 - 财政年份:2022
- 资助金额:
$ 154.65万 - 项目类别:
Project 3: In vitro modeling to define mechanisms of childhood vaccine response, susceptibility to respiratory infectious disease and asthma
项目 3:体外建模以确定儿童疫苗反应、呼吸道传染病和哮喘易感性机制
- 批准号:
10435043 - 财政年份:2022
- 资助金额:
$ 154.65万 - 项目类别:
Administrative Core: IDEAL shapes vaccine response, susceptibility to respiratory infectious disease and asthma
管理核心:IDEAL 影响疫苗反应、呼吸道传染病和哮喘的易感性
- 批准号:
10435036 - 财政年份:2022
- 资助金额:
$ 154.65万 - 项目类别:
Administrative Core: IDEAL shapes vaccine response, susceptibility to respiratory infectious disease and asthma
管理核心:IDEAL 影响疫苗反应、呼吸道传染病和哮喘的易感性
- 批准号:
10589801 - 财政年份:2022
- 资助金额:
$ 154.65万 - 项目类别:
IMPACC convalescent data collection, including Patient Reported Outcomes (PROs) and home visit sampling
IMPACC 恢复期数据收集,包括患者报告结果 (PRO) 和家访抽样
- 批准号:
10290547 - 财政年份:2021
- 资助金额:
$ 154.65万 - 项目类别:
IMPACC convalescent data collection, including Patient Reported Outcomes (PROs) and home visit sampling
IMPACC 恢复期数据收集,包括患者报告结果 (PRO) 和家访抽样
- 批准号:
10205742 - 财政年份:2021
- 资助金额:
$ 154.65万 - 项目类别:
Newborn cohorts to discover and validate biomarkers of neonatal vaccine immunogenicity
新生儿队列发现和验证新生儿疫苗免疫原性的生物标志物
- 批准号:
10323182 - 财政年份:2020
- 资助金额:
$ 154.65万 - 项目类别:
Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity
识别新生儿疫苗免疫原性生物标志物的系统生物学
- 批准号:
10221106 - 财政年份:2020
- 资助金额:
$ 154.65万 - 项目类别:
Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity
识别新生儿疫苗免疫原性生物标志物的系统生物学
- 批准号:
10265669 - 财政年份:2020
- 资助金额:
$ 154.65万 - 项目类别:
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